title: Novel 3,4-disubstituted-Neu5Ac2en derivatives as probes to investigate flexibility of the influenza virus sialidase 150-loop.
abstract: Novel 3,4-disubstituted-Neu5Ac2en derivatives have been synthesised to probe the open 150-loop conformation of influenza virus sialidases. Both equatorially and axially (epi) substituted C4 amino and guanidino 3-(p-tolyl)allyl-Neu5Ac2en derivatives were prepared, via the 4-epi-hydroxy derivative. The equatorially-substituted 4-amino derivative showed low micromolar inhibition of both group-1 (pdm09 H1N1) and group-2 (pdm57 H2N2) sialidases, and provides the first in vitro evidence that a group-2 sialidase may exhibit 150-loop flexibility.
authors.affiliation: Institute for Glycomics, Griffith University, Gold Coast Campus, Queensland 4222, Australia.
authors.forename: Santosh
authors.initials: S
authors.lastname: Rudrawar
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Dyason
authors.forename: Andrea
authors.initials: A
authors.lastname: Maggioni
authors.forename: Robin J
authors.initials: RJ
authors.lastname: Thomson
authors.forename: Mark
authors.initials: M
authors.lastname: von Itzstein
mesh_terms: D015335:Molecular Probes; D019158:N-Acetylneuraminic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D009439:Neuraminidase / Q000737:chemistry / Q000378:metabolism*; D009975:Orthomyxoviridae / Q000201:enzymology*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D012794:Sialic Acids / Q000737:chemistry*
chemical_list: D015335:Molecular Probes; D012794:Sialic Acids; C036137:2-deoxy-2,3-dehydro-N-acetylneuraminic acid; D009439:Neuraminidase; D019158:N-Acetylneuraminic Acid
keywords: 150-loop; Influenza; Neu5Ac2en; Sialic acid; Sialidase